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<div  id='write'  class = 'is-mac'><h1><a name='header-c5' class='md-header-anchor '></a>三代测序研究焦点⓵微生物&amp;传染性疾病</h1><div class='md-toc' mdtype='toc'><p class="md-toc-content"><span class="md-toc-item md-toc-h1" data-ref="c5"><a class="md-toc-inner" style="" href="#header-c5">三代测序研究焦点⓵微生物&amp;传染性疾病</a></span><span class="md-toc-item md-toc-h2" data-ref="c8"><a class="md-toc-inner" style="" href="#header-c8">探索隐藏的微生物世界</a></span><span class="md-toc-item md-toc-h3" data-ref="c11"><a class="md-toc-inner" style="" href="#header-c11">推进微生物学发展</a></span><span class="md-toc-item md-toc-h3" data-ref="c54"><a class="md-toc-inner" style="" href="#header-c54">微生物与公共卫生</a></span><span class="md-toc-item md-toc-h4" data-ref="c59"><a class="md-toc-inner" style="" href="#header-c59">局部信息已不能满足需要</a></span><span class="md-toc-item md-toc-h4" data-ref="c62"><a class="md-toc-inner" style="" href="#header-c62">得到更完整的病原微生物基因组</a></span><span class="md-toc-item md-toc-h4" data-ref="c81"><a class="md-toc-inner" style="" href="#header-c81">SMRT测序在公共卫生方面的应用</a></span><span class="md-toc-item md-toc-h3" data-ref="c102"><a class="md-toc-inner" style="" href="#header-c102">工业微生物学</a></span><span class="md-toc-item md-toc-h4" data-ref="c109"><a class="md-toc-inner" style="" href="#header-c109">先进的生物技术研发与微生物基因组&amp;群落的表征</a></span><span class="md-toc-item md-toc-h2" data-ref="c143"><a class="md-toc-inner" style="" href="#header-c143">参考文献</a></span></p></div><h2><a name='header-c8' class='md-header-anchor '></a>探索隐藏的微生物世界</h2><p>微生物构成了所有生命的基础，但我们只是刚开始认识到它们的重要性、丰富性和多样性。对完整的微生物表征来说，需要基因组的拼装和复杂序列、基因簇、可移动组分、甲基化的高分辨率解析，也需要对源自于各种组织、个体、甚至物种的混合体的序列进行去卷积。科学家们通过提高对上述内容的理解，可以微生物制品提供更好的设计与鉴定方法，也能够为全球卫生的改善提供支持。</p><h3><a name='header-c11' class='md-header-anchor '></a>推进微生物学发展</h3><p></p><p><img src='http://www.pacb.com/wp-content/uploads/2015/06/Icons_Fungal.png' alt='' /></p><p>——通过新的研究发现推进微生物学的发展</p><p>只有通过完整地表征微生物基因组、微生物群落以及它们与宿主和环境之间的相互关系，才能提高我们对微生物世界及其相互间联系的理解。</p><p>通过连续的Long-read和单分子分辨率的单分子实时（SMRT）测序，可以对我们周围的微生物群落进行前所未有的详细描述。 这种深入的观察允许科学家构建完整的微生物基因组、检测甲基化、剖析复杂的群落，以调查微生物生态学和微生物进化。</p><p>借助Sequel系统，科学家能够获得以下能力，更深入地了解微生物和微生物群落：</p><ul><li>彻底解决微生物基因组和移动成分的细节</li><li>检测表观遗传修饰</li><li>调查病毒致病性、进化和选择</li><li>了解微生物宏基因组和微生物群落</li><li>发现新基因和转录本同种型</li></ul><p><strong>特色研究：</strong>双相表观遗传开关调节流感嗜血杆菌中的免疫逃避[<a href='#ref1'>1</a>]</p><p><img src='http://www.pacb.com/wp-content/uploads/2015/08/Advancing_Microbiology.Biphasic_eipgenetic_switch.jpg' alt='' /></p><blockquote><p>非典型流感嗜血杆菌（Non-typeable <em>Haemophilus influenzae</em>）感染与儿童中耳感染、社区获得性肺炎（Community-Acquired Pneumonia）和慢性阻塞性肺（Chronic Obstructive Pulmonary）疾病显着相关。 在这个研究中，科学家已经使用流感嗜血杆菌的SMRT基因组和甲基化分析来发现表观遗传调控的开关，其调节免疫逃避（Immune Evasion）、抗生素抗性（Antibiotic Resistance）和生物膜形成（Biofilm Formation）中多个重要基因的表达。<a href='http://www.nature.com/ncomms/2015/150728/ncomms8828/abs/ncomms8828.html'>了解更多</a></p></blockquote><p><strong>特色研究：</strong>甲型流感中的复杂连锁和重配模式[<a href='#ref2'>2</a>]</p><p><img src='http://www.pacb.com/wp-content/uploads/2015/08/Advancing_Microbiology.Complex_linkage_and_reassortment_patterns.jpg' alt='' /></p><blockquote><p>使用单分子测序，H3N2甲型流感病毒群体的突变谱记录了抗病毒药物抗性进化的复杂变化。 该图显示了甲型流感片段HA、M、NA和NP以及跨时间点的共有（a）和单倍型（b）频率的谱系动力学示意图。<a href='http://mbio.asm.org/content/6/2/e02464-14?related-urls=yes&legid=mbio;6/2/e02464-14'>了解更多</a></p></blockquote><h3><a name='header-c54' class='md-header-anchor '></a>微生物与公共卫生</h3><p><img src='http://www.pacb.com/wp-content/uploads/2015/06/Icon_Virus.png' alt='' /></p><p>——通过对食品供应和人类健康的全面监测来改善公共卫生</p><h4><a name='header-c59' class='md-header-anchor '></a>局部信息已不能满足需要</h4><p>通过全面监测、完整基因组信息和精确追踪来保护全球健康（Global Health）是最好的方式。能够对致病微生物进行常规测序代表着相关技术的巨大进步。</p><h4><a name='header-c62' class='md-header-anchor '></a>得到更完整的病原微生物基因组</h4><p>SMRT测序的出现大大增加了对微生物基因组学、致病性和耐药性的理解。 Sequel系统能够提供最全面的遗传信息，可提供如下能力：</p><ul><li>深入了解Community-Acquired Illness</li><li>准确描述全球疫情（Global Outbreaks, Pandemics, and Epidemics）</li><li>指导局部地区和全球对季节和年度流行病的准备和应对</li><li>识别医院内疾病及其传播和来源</li><li>进行食源性病原体的监测和跟踪</li></ul><h4><a name='header-c81' class='md-header-anchor '></a>SMRT测序在公共卫生方面的应用</h4><ul><li>微生物全基因组测序</li><li>微生物基因组甲基化检测</li><li>解析复杂群体</li><li>解析病毒群体</li></ul><p><strong>特色研究：</strong>使用下一代多位点序列分型（Next Generation Multilocus Sequence Typing，NGMLST）表征一种条件致病真菌[<a href='#ref3'>3</a>]</p><p><img src='http://www.pacb.com/wp-content/uploads/2015/08/Microbes_in_Public_Health.Next_Generation_multilocus_sequence_typing.jpg' alt='' /></p><blockquote><p>新型隐球菌（<em>Cryptococcus neoformans</em>）是一种Well-characterized人条件致病真菌病原体，在全世界范围内造成&gt; 500,000人死亡。 使用Cost-effective、Well-characterized新MLST方法对分离株进行基因分型，其利用了SMRT测序、多路复用的方案以及合适的分析软件，其在单次测定中提供96个或更多分离株的准确、快速、经济的基因分型。 上图通过相邻连接的树状图可视化具有不同分子类型的分离株和6个杂种的两个等位基因的SOD1基因座的系统发育。<a href='http://www.sciencedirect.com/science/article/pii/S1087184515000080'>了解更多</a></p></blockquote><h3><a name='header-c102' class='md-header-anchor '></a>工业微生物学</h3><p><img src='http://www.pacb.com/wp-content/uploads/2015/06/Icons_Bacteria.png' alt='' /></p><p>——通过不断发展的工业微生物学解决当今面临的全球挑战</p><p>现代制药学发现，环境治理和化学商品生产越来越依赖于对微生物的利用。为了识别和开发复杂的生物制品，微生物学家非常需要综合的基因组信息。基于二代测序（短读长）的微生物基因组草图组装算法常会丢失一些关键基因或者代谢相关基因簇片段。这些不完整的组件可能对功能基因组学研究和基因组工程的工作产生限制甚至造成破坏。此外，基因组草图不提供有关限制修饰（Restriction-Modification，R-M）系统的信息；没有这些信息，不匹配的质粒DNA在遗传操作过程中的转化率可能就会比较低。</p><h4><a name='header-c109' class='md-header-anchor '></a>先进的生物技术研发与微生物基因组&amp;群落的表征</h4><p>SMRT测序的出现为个体微生物和微生物群落提供了更全面的研究手段，借助Sequel系统，科学家们将有能力：</p><ul><li>为工业上很重要的微生物构建完整的基因组组装，重建完整基因序列，发现新的基因簇</li><li>探讨表观遗传调控如何提高微生物遗传操控的效率</li><li>确定复杂微生物群落的关键成员，以分离和开发商业微生物产品</li><li>解析病毒种群，以便成功设计和评估药物和疫苗</li><li>获得转录本和宏转录组的完整序列，直接定义产生重要工业微生物产物的全长操纵子</li><li>靶向验证</li></ul><p><strong>特色研究：</strong>产乙醇梭菌（Clostridium <em>autoethanogenum</em>）的完整基因组有助于准确推断关键代谢途径[<a href='#ref4'>4</a>]</p><p><img src='http://www.pacb.com/wp-content/uploads/spotlight1-industrial-microbiology.jpg' alt='' /></p><p>该文研究了一种能够将废气发酵成生物燃料和化学商品的微生物：产乙醇梭菌的工业菌株。研究者单纯使用SMRT测序数据进行的基因组组装。 他们对组装的分析显示，在以前利用Short-read组装的基因组草图中，有许多在代谢上很重要的基因已经完全丢失或仅被部分覆盖。<a href='http://www.biotechnologyforbiofuels.com/content/7/1/40'>了解更多</a></p><p><strong>特色研究：</strong>鉴定动物双歧杆菌（<em>Bifidobacterium animalis</em>）中的限制性修饰系统[<a href='#ref5'>5</a>]</p><p><img src='http://www.pacb.com/wp-content/uploads/spotlight2-industrial-microbiology.jpg' alt='' /></p><p>科学家们使用SMRT测序来构建已知含有有益健康的（商业化发酵乳制品的）组分的动物双歧杆菌的完整基因组并检测其甲基化。 R-M系统一直是双歧杆菌遗传操作的主要障碍。 SMRT测序预测这种双毛杆菌菌株携带两个R-M系统（BanLI和Ban LII）。 通过使用适当的甲基化质粒DNA，与未甲基化的DNA相比，转化效率提高达22倍。<a href='http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094875'>了解更多</a></p><h2><a name='header-c143' class='md-header-anchor '></a>参考文献</h2><p><span id="ref1">[1] Atack et al., (2015) A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae. Nature Communications. 6(7828).</span></p><p><span id="ref2">[2] Rogers M., et al., (2015) Intrahost dynamics of antiviral resistance in influenza A virus reflects complex patterns of segment linkage, reassortment, and natural selection. mBio. 6(2), e02464-14.</span></p><p><span id="ref3">[3] Chen, Y., et al., (2015) Next generation multilocus sequence typing (NGMLST) and the analytical software program MLSTEZ enable efficient, cost-effective, high-throughput, multilocus sequencing typing. Fungal Genetics and Biology.75, 64-71.</span></p><p><span id="ref4">[4] Brown et al., (2014) Comparison of single-molecule sequencing and hybrid approaches for finishing the genome of Clostridium autoethanogenum and analysis of CRISPR systems in industrial relevant Clostridia. Biotechnology for Biofuels. 7, 40.</span></p><p><span id="ref5">[5] Motherway et al., (2014) Identification of Restriction-Modification Systems of Bifidobacterium animalis subsp. lactis CNCM I-2494 by SMRT Sequencing and Associated Methylome Analysis. PLoS One. 9(4) E94875</span></p></div>
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